DDMAC Targets ADHD Products – FDA Issues Five Warning Letters on the Same Day

September 29, 2008

We previously reported (April 25, 2007, May 22, 2007, August 14, 2007) on a trend in policing promotional and advertising claims by FDA’s Division of Drug Marketing, Advertising, and Communications (“DDMAC”), in which DDMAC has focused on ensuring that all claims are supported by substantial evidence and that all safety data are properly presented.On September 25, 2008, this pattern re-emerged as FDA issued Warning Letters to five manufacturers of Attention Deficit Hyperactivity Disorder (“ADHD”) drug products.DDMAC’s top concerns?Promotional statements that broadened the drugs’ claims and overstated their efficacy without the requisite substantial evidence or “substantial clinical experience” to support them.This dovetails with the caution we issued last year:that substantial evidence was the “watchword” for companies trying to avoid running afoul of DDMAC.Interestingly, these five letters target a particular therapeutic class – ADHD products – and for claims made in a range of material, from sales aids to a video featuring Ty Pennington posted on youtube.com.

Drug was misbranded under 21 U.S.C. §§ 352(a), 352(n), and 321(n) by promotional claims included on convention panels and a webpage that:

(1) Overstated its efficacy; and

(2) Omitted facts.

Focalin XR® extended-related capsules

(Novartis)

Drug was misbranded under 21 U.S.C. §§ 352(a) and 352(n) by promotional claims included on a professional slide deck and webpage that:

(1) Overstated its efficacy; and

(2) Broadened its indication.

Methylin® chewable tablets and oral solution (Mallinckrodt)

Drug was misbranded under 21 U.S.C. §§ 352(a) and 321(n) by promotional claims included on a patient brochure that:

(1) Overstated its efficacy;

(2) Omitted and/or minimized risk information; and

(3) Made unsubstantiated claims, including comparative claims.

Strattera®

(Eli Lilly)

Drug was misbranded under 21 U.S.C. §§ 352(a) and 321(n) by promotional claims included on a professional sales aid that:

(1) Overstated its efficacy;

(2) Broadened its indication;

(3) Omitted material fact; and

(4) Minimized risk information.

(3) Omitted material fact; and

(4) Minimized risk information.

The conclusion that the companies had overstated the efficacy and broadened the indications of their drugs rested mainly on material that discussed the consequences of not treating ADHD in teenagers and adults.For example, a Shire web page listed “[d]ifficulties caused by ADHD in adolescence” when left untreated, which included “academic problems,” “difficulty maintaining friendships,” “impulsive behavior,” and sexual promiscuity.The Agency concluded that the references Shire cited did not support these statements, rendering the claims misleading, because they implied that the drug prevented these ADHD “side effects” without substantial evidence.In one example, FDA stated that although a study Shire cited examined the “academic and social outcomes in young adults diagnosed with ADHD” it failed to “study the effects of drug treatment on those outcomes.”

FDA made similar conclusions about the claims made by Eli Lilly, Novartis, and Mallinckrodt about the consequences of untreated ADHD. This begs the question of whether DDMAC is being overly cautious in its review of the claims for this drug class, one company simply pushed the proverbial promotional envelop too far and other companies followed suit, or if DDMAC is clamping down even harder on studies purported to be substantial evidence of promotional claims.In any event, these Warning Letters serve as another important reminder that DDMAC demands a high level of “substantial evidence” in support of promotional claims.